Department of Immunology, College of Medicine, Yanbian University, Yanji.
Department of Spine Surgery, Jilin Central Hospital, Jilin City.
Anticancer Drugs. 2022 Aug 1;33(7):607-613. doi: 10.1097/CAD.0000000000001276. Epub 2022 Apr 29.
Osteosarcoma serves as frequently occurred bone malignancy that displays low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been reported as the crucial molecules in osteosarcoma development. However, the effect of circRNA circMRPS35 on osteosarcoma remains unclear. Here, we aimed to explore the function of circMRPS35 in the regulation of autophagy and progression of osteosarcoma. The colony formation numbers and Edu-positive osteosarcoma cells were repressed by the overexpression of circMRPS35. Meanwhile, the overexpression of circMRPS35 increased the apoptosis rate of osteosarcoma cells. The expression levels of autophagy markers, including LC3 and Beclin1, were enhanced by the overexpression of circMRPS35 in osteosarcoma cells. Mechanically, the depletion of circMRPS35 reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) on forkhead box O3 (FOXO3) promoter in osteosarcoma cells. The interaction of circMRPS35 and KAT6B was identified. The knockdown of KAT6B reduced the enrichment of H3K23ac on FOXO3 promoter in osteosarcoma cells. The depletion of circMRPS35 repressed the expression of FOXO3 in the MG63 and MNNG/HOS cells, whereas the overexpression of KAT6B reversed the effect. Significantly, KAT6B promotes apoptosis and autophagy of osteosarcoma cells. The overexpression of circMRPS35 induced the apoptosis and autophagy of osteosarcoma cells, in which the depletion of KAT6B or FOXO3 reversed the effect. The overexpression of circMRPS35 inhibited the tumor growth in vivo , whereas the depletion of KAT6B could reverse the effect in the mice. Therefore, we concluded that circRNA circMRPS35 repressed progression and induced autophagy of osteosarcoma cells.
骨肉瘤是一种常见的骨恶性肿瘤，其生存率低，转移率高。环状 RNA（circRNA）已被报道为骨肉瘤发生发展的关键分子。然而，circRNA circMRPS35 对骨肉瘤的影响尚不清楚。在这里，我们旨在探讨 circMRPS35 在调节骨肉瘤自噬和进展中的作用。circMRPS35 的过表达抑制了集落形成数量和 Edu 阳性骨肉瘤细胞。同时，circMRPS35 的过表达增加了骨肉瘤细胞的凋亡率。circMRPS35 在骨肉瘤细胞中的过表达增强了自噬标记物 LC3 和 Beclin1 的表达水平。在机制上，circMRPS35 的耗竭降低了骨肉瘤细胞中叉头框 O3（FOXO3）启动子上组蛋白 H3 赖氨酸 23 乙酰化（H3K23ac）的富集。鉴定到 circMRPS35 和 KAT6B 的相互作用。KAT6B 的敲低降低了骨肉瘤细胞中 FOXO3 启动子上 H3K23ac 的富集。circMRPS35 的耗竭抑制了 MG63 和 MNNG/HOS 细胞中 FOXO3 的表达，而 KAT6B 的过表达则逆转了这种作用。重要的是，KAT6B 促进骨肉瘤细胞的凋亡和自噬。circMRPS35 的过表达诱导了骨肉瘤细胞的凋亡和自噬，而 KAT6B 或 FOXO3 的耗竭则逆转了这种作用。circMRPS35 的过表达抑制了体内骨肉瘤的生长，而 KAT6B 的耗竭则可以在小鼠中逆转这种作用。因此，我们得出结论，circRNA circMRPS35 抑制骨肉瘤的进展并诱导其自噬。
